OLP组织中Smad7蛋白的表达研究

目的:检测Smad7蛋白在口腔扁平苔藓(OLP)组织中的表达及分布,探讨其在OLP发病机制中的作用。方法:采用免疫组化SABC法,用Smad7兔抗人多克隆抗体检测60例OLP病变组织及10例正常口腔黏膜组织中Smad7蛋白的表达及分布。结果:Smad7在OLP病变组织有明显的阳性表达,而在正常口腔黏膜组织中阴性表达(P<0.05)。结论:Smad7蛋白在OLP病变组织中高表达,其在OLP发病机制中有重要作用。     

K_v3.4在口腔扁平苔藓和口腔鳞状细胞癌中的表达

目的:研究钾离子通道蛋白kv3.4在正常口腔黏膜(normal oral mucosa,NOM)、口腔扁平苔藓(oral lichen planus,OLP)、口腔鳞状细胞癌(squamous cell carcinoma,OSCC)中的表达及意义。方法:免疫组织化学技术检测16例NOM、20例OLP和30例OSCC组织中kv3.4的表达,采用Wilcoxon秩和检验,α=0.05。结果:kv3.4在OSCC中的表达强度高于OLP(P<0.05),kv3.4在OLP组织的表达高于正常组织(P<0.05),且糜烂型OLP中的表达高于非糜烂型OLP(P<0.05),差异均具有统计学意义。结论:kv3.4可能与OLP及OSCC的发生、发展有一定的关系。     

Expression of caspase-3 and structural changes associated with apoptotic cell death of keratinocytes in oral lichen planus

OBJECTIVE: Apoptosis appears to be the mode of cell death by which damaged cells are removed from the lesional tissue. The aim of this study was to examine keratinocyte apoptosis and caspase-3 (CPP32) expression in oral lichen planus (OLP). MATERIALS AND METHODS: Paraffin-embedded samples of OLP (n = 30) and normal oral mucosa (NOM; n = 5) were prepared for haematoxylin-eosin (H & E), immunohistochemistry and electron microscopy. The number of apoptotic cells and the proportion of total cells that were either apoptotic (apoptotic index; AI) or mitotic (mitotic index; MI) were assessed in H & E stained sections. An immunostaining-intensity-distribution index (IIDI; proportion of stained cells x staining intensity) was used to assess CPP32 immunoreactivity. RESULTS: Results showed a significant increase in the number of apoptotic cells in OLP (P < 0.001). In OLP, all apoptotic bodies were found in the basal and prickle epithelial layers. Compared with NOM, the AI was significantly greater in atrophic (P < 0.05), reticular (P < 0.001) and plaque-like (P < 0.01) OLP. The MI was significantly greater in plaque-like OLP (P < 0.01). The proportion of CPP32-positive cells and the IIDI were significantly greater in all forms of OLP compared with NOM (P < 0.05). No difference in CPP32 expression was evident between clinical forms of OLP. Electron microscopy confirmed the light microscopic finding of apoptosis. CONCLUSION: Keratinocyte apoptosis and caspase-3 expression co-localized to the basal and parabasal epithelial layers, suggesting that proliferating epithelial cells may be targeted for destruction in OLP. Differences in epithelial AI and MI may underlie the various clinical and histological appearances of OLP.     

VCAM-1 and ICAM-1 are expressed by Langerhans cells, macrophages and endothelial cells in oral lichen planus

Expression of intercellular adhesion molecule-1 (ICAAM-1, CD54) and vascular cell adhesion molecule-1 (VCAM-l, CD106) was examined in oral lichen planus (OLP) and normal oral mucosa (NOM). Immunoperoxidase staining showed ICAM-1 expression by vascular endothelium in all biopsies of OLP and NOM whereas endothelial VCAM-l staining was found in 2/7 NOM and 8/9 OLP. In the lamina propria of NOM occasional cells were ICAM-1 or VCAM-l positive, and virtually no staining of intraepilhelial dendritic cells was seen for either marker. Intraepithelial dendritic cells stained for ICAM-1 in 7/9 and VCAM-1 in 4/9 OLP biopsies. Double immunofluorescence showed dual labelling of Langerhans cells (LC) with CD1a and VCAM-l in a further 5/12 cases of OLP, but there was no such staining in four NOM. This is the first report of LC staining with VCAAM-l. Induction of ICAM-1 and VCAM-l on LC and macrophages in OLP suggests these cells are activated and may contribute to the pathogenesis of OLP by presenting antigen to infiltrating lymphocytes.     

CD146 expression in oral lichen planus and oral cancer

Clinical Oral Investigations - To examine the CD146/METCAM expression on keratinocytes in normal oral mucosa (NOM), oral lichen planus (OLP), oral epithelial dysplasia (OED), and oral squamous cell...     

Erythematous and reticular forms of oral lichen planus and oral lichenoid reactions differ in pathological features related to disease activity

BACKGROUND: Common clinical forms of oral lichen planus (OLP) and oral lichenoid reactions (OLR) are erythematous (ERY) or reticular (RET). The purpose of this study was to find histopathological changes that differ between these forms. METHODS: Epithelial thickness, epithelial proliferation rate, apoptosis, and HLA-DR expression were compared among 10 reticular and 12 erythematous lesions, and 11 normal oral mucosa samples (NOM). RESULTS: The epithelium in ERY was thinner than in NOM, whereas RET showed values between ERY and NOM. Cell proliferation increased significantly in ERY as compared with RET and NOM, with no difference between RET and NOM. Relative numbers of epithelial cell nuclei displaying visible chromatin condensation were reduced in ERY form. CONCLUSIONS: The markedly increased cell proliferation in ERY supports the notion that this form displays a higher disease activity as compared to RET. It can therefore be important to study each disease form separately.     

P53 and bcl-2 immunoexpression in patients with oral lichen planus and oral squamous cell carcinoma

Objective: The aim of this study was to determine by immunohistochemistry the presence and significance of p53 and bcl-2 proteins in oral lichen planus (OLP) and oral squamous cell carcinoma (OSCC). Study Design: We used 21 cases diagnosed as OLP 16 diagnosed as OSCC and four normal gingival biopsies taken from healthy patients were used as controls. Slides were processed for immunohistochemistry using anti-p53 and anti-bcl-2 monoclonal antibodies. Results: We found p53 immunoexpression in 71.4% OLP cases and 68.7% OSCC cases, with no immunoexpression in control cases. Bcl-2 was negative for all OLP and OSCC cases, and mild positivity was observed in normal tissue. We found significant correlation among p53 expression and OSCC malignancy. Conclusions: Our results suggest that TP53 system mainly promotes a hyperproliferative state by cell cycle arrest of the OLP epithelial cells for repairing damaged DNA nor apoptosis and that anti-apoptotic action of bcl-2 is not important in this disease. Key words:Oral lichen planus, oral squamous cell carcinoma, p53, Bcl-2, carcinogenesis, malignant transformation.     

HERG1在口腔扁平苔藓和口腔鳞状细胞癌中的表达

目的：研究钾离子通道蛋白HERG1在正常口腔黏膜（normal oral mucosa,NOM）、口腔扁平苔藓（oral lichen planus,OLP）、口腔鳞状细胞癌（squamous cell carcinoma,OSCC）中的表达及意义。方法：免疫组织化学技术检测16例NOM、20例OLP、30例OSCC组织中HERG1的表达。采用χ2检验,P〈0.05为差异具有统计学意义。结果：HERG1在OSCC中的表达强度高于OLP（P〈0.05）,HERG1在OLP组织的表达高于正常组织（P〈0.05）,且糜烂型OLP中的表达高于非糜烂型OLP（P〈0.05）,差异均具有统计学意义。结论：HERG1可能与OLP及OSCC的发生发展有一定的关系。     

P53和Mdm2蛋白在人口腔扁平苔藓和口腔鳞状细胞癌中的表达

目的：探讨正常口腔黏膜组织（NOM）、口腔扁平苔藓（OLP）、口腔鳞状细胞癌（OSCC）组织中,抑癌基因P53和癌基因Mdm2的表达情况及关系。方法：采用免疫组化SP法检测12例正常口腔黏膜组织、40例OLP组织、33例OSCC组织中P53、Mdm2基因的表达情况,并分析其相关性。结果：P53蛋白在NOM、OLP及OSCC组织中的阳性表达率呈明显的逐渐升高趋势。Mdm2蛋白在NOM中不表达,在OLP中呈现弱阳性表达,在OSCC不同病理分级中阳性表达率依次增高。各组表达均有统计学意义（P〈0.05）。另外P53蛋白、Mdm2蛋白在OS-CC组织中的表达关系无明显的相关性。结论：P53、Mdm2蛋白的表达与OLP及OSCC的发生、发展密切相关。     

口腔黏膜扁平苔藓患者口腔黏膜组织中cyclin D1,ki-67及凋亡的表达研究

目的　检测口腔黏膜扁平苔藓 (OLP)患者口腔黏膜上皮凋亡增殖状况及细胞周期调控蛋白表达水平的变化 ,探讨OLP发病机制。方法　采用甲基绿 -派诺宁法及免疫组化SABC法分别检测 30例OLP患者及 2 0例正常对照者口腔黏膜组织的凋亡情况及细胞周期蛋白 (cyclinD1)、增殖细胞核抗原 (ki 6 7)的表达并进行细胞计数及统计学分析。结果　OLP组与对照组凋亡、ki 6 7、cyclinD1表达阳性率差异有显著性 (P <0 .0 5 ) ;与凋亡呈正相关。结论　OLP病变中 ,部分细胞受损进入凋亡性细胞死亡 ,同时发生了细胞周期紊乱、细胞增殖     

凋亡蛋白Bcl-2、Bax在白斑、口腔扁平苔藓中的表达

目的:观察凋亡蛋白Bcl-2、Bax在白斑、口腔扁平苔藓上皮细胞中的表达,探讨其在口腔白斑、口腔扁平苔藓癌变过程中的作用机制。方法:采用免疫组化法检测10例正常口腔黏膜上皮、18例口腔扁平苔藓、23例白斑、22例口腔鳞癌上皮组织中凋亡相关蛋白Bcl-2、Bax的表达水平。结果:Bcl-2在白斑、口腔扁平苔藓上皮细胞层无异常表达,但在口腔扁平苔藓淋巴细胞浸润带过度表达。Bcl-2在鳞癌组织中呈高表达,与正常黏膜相比有显著性差异(P<0.05)。Bax在上皮单纯增生、轻度、中度不典型增生和低分化鳞癌及糜烂型口腔扁平苔藓组织中呈过度表达,与正常黏膜相比有显著性差异(P<0.05)。结论:Bax参与了口腔白斑癌变的早期事件,而Bcl-2在不典型增生转化为鳞癌的阶段并未发生作用。口腔扁平苔藓的发病机制可能与Bcl-2抑制淋巴细胞凋亡,使细胞免疫亢进,从而刺激上皮细胞Bax过度表达,诱导角朊细胞凋亡有关。     

Activation of nuclear factor-kappa B correlates with tumor necrosis factor-alpha in oral lichen planus: a clinicopathologic study in atrophic-erosive and reticular form

Backgroud:  Nuclear factor-kappa B (NF-κB) is believed to be involved in the pathogenesis of various inflammatory diseases, including oral lichen planus (OLP). The objective of the present study was to investigate the possible relationship between NF-κB activation and expression of tumor necrosis factor-alpha (TNF-α) in OLP and their expression pattern in relation to several clinical features.
Methods:  Thirty OLP cases were divided into atrophic-erosive form (14 cases) and reticular form (16 cases) according to their clinical manifestations. The expression of NF-κB p65 and TNF-α of both two groups were investigated by immunohistochemical staining, and the percentage of positive cells was calculated in each case. Biopsies of 10 normal oral mucosa (NOM) also underwent the same procedure as controls.
Results:  Nuclear factor-kappa B p65 nuclear staining was found in nuclei of basal and suprabasal epithelial keratinocytes in OLP, however, no positive staining was found in NOM. Positive TNF-α staining was detected in cytoplasm of basal epithelial keratinocytes in OLP, and only scattered staining was detected in NOM. Expression of NF-κB p65 and TNF-α were significantly different with respect to clinical forms and lesion sites ( P  < 0.05), except for genders ( P  > 0.05) in 30 OLP cases. NF-κB nuclear staining positively correlated ( r  = 0.676, P  < 0.01) with TNF-α overexpression in OLP.
Conclusions:  Nuclear factor-kappa B activation and its correlation with overexpression of TNF-α may play an important role in pathogenesis of OLP. There might be a positive regulatory loop between NF-κB and TNF-α, which may contribute to inflammation in OLP; NF-κB may also protect epithelial keratinocytes from excessive apoptosis.     

热休克蛋白60、70在口腔扁平苔藓中表达的研究

目的　探讨热休克蛋白 (heatshockprotein ,HSP) 60和HSP70在口腔扁平苔藓病变中的作用。方法　对 62例口腔扁平苔藓、1 0例正常口腔粘膜、2 1例慢性盘状红斑狼疮、1 0例粘膜良性淋巴组织增生病 ,46例白斑进行免疫组织化学SP法染色 ,分析HSP60、HSP70在口腔扁平苔藓中的表达 ;对 1 2例口腔扁平苔藓和 5例正常粘膜进行逆转录PCR实验 ,观察HSP60、HSP70mRNA的变化。结果　HSP60在口腔扁平苔藓病损区的表达较其他各组显著增强 ,差异有显著性 (P <0 0 0 1 )。HSP70在糜烂型口腔扁平苔藓病损区的表达下调。RT PCR结果显示 ,HSP60、HSP70mRNA表达增强。结论　HSP60及HSP70在口腔扁平苔藓的发病中起重要作用     

FOXP3和GITR在口腔扁平苔藓及口腔鳞状细胞癌中的表达及意义

目的研究FOXP3、GITR在口腔扁平苔藓（OLP）和口腔鳞状细胞癌（OSCC）组织中的表达及其意义。方法采用免疫组化方法检测30例OLP组织、30例OSCC组织和15例口腔正常黏膜（NOM）组织中FOXP3、GITR的表达。结果NOM组FOXP3和GITR阴性表达;OLP组和OSCC组FOXP3和GITR表达分别较NOM组显著增加（P〈0.01）;OLP组和OSCC组之间FOXP3和GITR表达无显著性差异（P〉0.05）;FOXP3和GITR在OLP组和OSCC组中的表达存在正相关关系。结论在OLP的发生及发展成OSCC过程中,FOXP3和GITR均可能起着一定的作用。     

MMP-28在复发性阿弗他溃疡、口腔扁平苔藓、口腔白斑中的表达和意义的研究

目的　探讨MMP-28在复发性阿弗他溃疡、口腔扁平苔藓、口腔白斑中的表达和意义。方法　分别采用免疫组化和Western-blot方法检测MMP-28在14例复发性阿弗他溃疡、16例口腔扁平苔藓、15例口腔白斑病中的表达,并与12例正常口腔黏膜进行比较。结果　口腔扁平苔藓、口腔白斑组织中MMP-28的表达高于正常口腔黏膜和复发性阿弗他溃疡组织,白斑组织中表达高于扁平苔藓组织。结论　MMP-28在口腔扁平苔藓、白斑患者中有表达,且在白斑患者中高表达,提示其可能参与了癌变的发病过程。     

T细胞免疫和细胞凋亡在口腔扁平苔藓发病中的作用

目的通过探讨口腔扁平苔藓（OLP）中细胞凋亡情况及CD4＋、CD8＋T细胞和CD4/CD8比例的变化分析细胞免疫与细胞凋亡的关系,进一步了解OLP的发病机制。方法应用免疫组化SP法检测27例OLP组织中CD4＋、CD8＋T细胞的表达水平,并用原位末端转移酶标记法（TUNEL）定位检测17例OLP中细胞凋亡情况。结果OLP组固有层中CD4＋、CD8＋T细胞明显高于对照组（P＜0.05）,CD4/CD8值降低。OLP组中上皮内细胞凋亡指数高于对照组,固有层淋巴细胞凋亡指数明显低于对照组。结论OLP组固有层中CD4＋、CD8＋T细胞浸润的增加、CD4/CD8比值的变化及OLP中上皮细胞和固有层淋巴细胞凋亡异常,说明细胞免疫功能紊乱和细胞凋亡异常在OLP发病中起重要作用。     

Changes in the expression of stem cell markers in oral lichen planus and hyperkeratotic lesions

Despite the pivotal role of stem cells in homeostasis of oral epithelia the location of this cell population within the tissue is uncertain. How disease influences these cells in vivo also remains to be elucidated. In this study we have used six molecular markers to identify stem cells in normal and diseased buccal mucosa. Samples of normal oral mucosa (NOM), hyperkeratosis (OHK) and oral lichen planus (OLP) were immunostained for alpha6 and beta1 integrins, keratin 15 (K15), melanoma-associated chondroitin sulphate proteoglycan (MCSP), NG2 the rat homologue of human MCSP and notch 1. K15, NG2 and beta1 staining was continuous in the basal layer of NOM whilst alpha6 and MCSP were limited to basal cells at the tips of connective tissue papillae. K15 was downregulated in OLP whereas alpha6, beta1 and MCSP were upregulated in both OLP and OHK. NG2 remained unchanged and notch 1 was absent in all samples. Therefore, the stem cell phenotype in OLP and OHK maybe altered in response to pathological signaling. Classification of these changes is essential to understand the role of adult stem cells in the pathogenesis of oral diseases characterised by abnormal keratinocyte proliferation and differentiation.     

IL-2、IL-1O在口腔扁平苔藓发病中的作用

目的：通过对口腔扁平苔藓（OLP）局部组织及外周血中IL-2、IL-10表达进行研究,进-步探讨OLP发病机制。方法：应用免疫组织化学SABC法检测30例OLP中IL-2、IL-10的表达数量及分布,同时用ELISA法检测外周血中IL-2、IL-10的含量。结果：①在病损组织中,OLP组中IL-2、IL-10表达显著高于对照组（P〈0．05）。IL-2主要分布在淋巴细胞浸润带,在基底膜附近较集中;IL-10主要分布在固有层,远离基底膜。②在外周血中,糜烂型OLP组IL-2、IL-10含量明显高于对照组和非糜烂型OLP组（P〈O．05）。结论：①根据IL-2、IL-10在OLP中表达和分布情况,提示IL-2、IL-10在OLP发病机制中参与了机体免疫的调节和介导作用。②外周血中IL-10高表达,提示糜烂型OLP患者全身的免疫反应参与了本病的形成或可能伴有全身免疫系统功能紊乱。     

口腔癌前病变细胞凋亡状况及Bcl-2、Bax表达的研究

目的 :通过对口腔白斑、扁平苔藓病变发展及癌变过程中细胞凋亡状况和凋亡相关蛋白表达水平的研究 ,探讨口腔白斑、扁平苔藓的癌变机理及病变机制。方法 :采用原位末端转移酶标记法及免疫组化法 ,观察分析 10例正常口腔黏膜上皮 ,18例扁平苔藓 ,2 3例白斑 ,2 2例口腔鳞癌上皮组织中细胞凋亡状况及凋亡相关蛋白Bcl- 2、Bax的表达水平。结果 :上皮 (轻 ,中 ,重 )不典型增生 ,鳞癌及糜烂型扁平苔藓的凋亡指数均高于正常 (P <0 .0 1)。Bcl- 2在白斑、扁平苔藓上皮细胞层无异常表达 ,但在扁平苔藓固有层淋巴细胞浸润处过度表达 ,在鳞癌组织中显高表达 (P <0 .0 1)。Bax在上皮单纯增生、轻、中度不典型增生和鳞癌及糜烂型扁平苔藓组织中显过度表达 (P <0 .0 5 )。结论 :白斑、扁平苔藓的病变发展及癌变过程中 ,上皮细胞凋亡状况发生了改变 ,Bax参与了白斑癌变的早期事件。扁平苔藓的发病机制与Bcl- 2、Bax在特定部位的过度表达有关